1. Field of the Invention
This invention relates to chemical analogs of the sweet glycoside, stevioside, which are themselves sweet and useful as sweeteners.
2. The Prior Art
The leaves of the Paraguayan shrub Stevia rebaudiana Bertoni have long been known to be sweet. A sweet crystalline glycoside has been isolated from these leaves. This compound, named Stevioside by the Union International de Chimie in 1921, has been reported to be about 300 times as sweet as sucrose by Bridel et al., Compt. Rend., 192, 1123-5 (1931) and J. Pharm. Chim., 14 (3), 99-113; 14 (4), 154-161 (1931). Mosettig et al. reported the absolute configuration of stevioside as ##STR2## in J. Am. Chem. Soc., 85, 2305-2309 (1963). This material has attracted substantial interest as a potential sweetener. (See Japanese Patents 51-52200; 52-47956, 7 and 9; 52-51069; 52-57198 and 9 and 52-62300.) To date, it has not been commercially adopted for two reasons. First, the sweet taste is contaminated with a substantial degree of bitterness (Bridel et al., above). Second, the compound is metabolically unstable. It undergoes enzymatic hydrolysis to the diterpenoid aglycone steviol, ##STR3## (R. Wingard, J. Dale, J. Brown, R. Hale, Experientia, 36, 519, (1980)), a tasteless material that exhibits undesirable physiological activities. Steviol is reported to be a potent inhibitor of ATP synthesis in mitochondria (Vignais, P. U. et al., Biochim. Biophys. Acta, 118, 465-483 (1966)) and also shows antiandrogenic effects (Dorfman, R. I., et al., Endocrinology, 67, 282-285 (1965).
Reported studies on stevioside have generally focused on its purification and the cultivation of its source. Little has been done to develop or discover analogs which present the desired sweetness without the troublesome disadvantages of bitterness and instability.